Role of innate host defense proteins in oral cancerogenesis.

It is nowadays well accepted that chronic inflammation plays a pivotal role in tumor initiation and progression. Under this aspect, the oral cavity is predestined to examine this connection because periodontitis is a highly prevalent chronic inflammatory disease and oral squamous cell carcinomas are the most common oral malignant lesions. In this review, we describe how particular molecules of the human innate host defense system may participate as molecular links between these two important chronic noncommunicable diseases (NCDs). Specific focus is directed toward antimicrobial polypeptides, such as the cathelicidin LL-37 and human defensins, as well as S100 proteins and alarmins. We report in which way these peptides and proteins are able to initiate and support oral tumorigenesis, showing direct mechanisms by binding to growth-stimulating cell surface receptors and/or indirect effects, for example, inducing tumor-promoting genes. Finally, bacterial challenges with impact on oral cancerogenesis are briefly addressed.

Consensus report of the second European Consensus Workshop on Education in Periodontology.

BACKGROUND: The second European Consensus Workshop on Education in Periodontology was commissioned, as a result of the changes in the discipline and the advances in educational methods/technology, to update the 2009 Consensus report of the first European Federation of Periodontology (EFP) Workshop on the same topic that was jointly authored by the Association for Dental Education in Europe. AIM: To identify and propose changes necessary in periodontal education at three levels, namely undergraduate, specialist and continuing professional development (CPD), with respect to learning outcomes, competencies and methods of learning/training and evaluation. METHODS: Four working groups (WGs) considered education in periodontology at the undergraduate, specialist and CPD levels, and education methods. Four commissioned position papers, one per WG, summarized the relevant information. Workshop participants gathered at an in-person consensus meeting to discuss the individual reviews, and this consensus report summarizes the conclusions. RESULTS: The learning outcomes for undergraduate and specialist education in periodontology have been updated, and a proposal for learning outcomes for CPD programmes was made. Learning/teaching/training and evaluation methods were proposed for each level of education, which included face-to-face, virtual and blended learning methods. CONCLUSION: Developments in oral/dental medicine and in contemporary educational technologies have been translated into updated learning outcomes and learning/teaching/ training/evaluation methods relevant to education in periodontology.

ACES: A new framework for the application of the 2018 periodontal status classification scheme to epidemiological survey data.

AIM: To propose a framework for consistently applying the 2018 periodontal status classification scheme to epidemiological surveys (Application of the 2018 periodontal status Classification to Epidemiological Survey data, ACES). PROPOSED FRAMEWORK: We specified data requirements and workflows for either completed or planned epidemiological surveys, utilizing commonly collected measures of periodontal status (clinical attachment levels [CAL], probing depths, bleeding on probing), as well as additional necessary variables for the implementation of the 2018 periodontal status classification (tooth loss due to periodontitis and complexity factors). Following detailed instructions and flowcharts, survey participants are classified as having periodontal health, gingivitis or periodontitis. Rates of edentulism must also be reported. In cases of periodontitis, instructions on how to compute the stage and extent are provided. Assessment of grade can be derived from CAL measurements (or from radiographic alveolar bone loss data) in relation to root length and the participant's age. CONCLUSIONS: ACES is a framework to be used in epidemiological studies of periodontal status that (i) have been completed, and in which stage and grade according to the 2018 classification are inferred retroactively, or (ii) are being planned. Consistent use of the proposed comprehensive approach will facilitate the comparability of periodontitis prevalence estimates across studies.

A genome-wide association study meta-analysis in a European sample of stage III/IV grade C periodontitis patients ≤35 years of age identifies new risk loci.

AIM: Few genome-wide association studies (GWAS) have been conducted for severe forms of periodontitis (stage III/IV grade C), and the number of known risk genes is scarce. To identify further genetic risk variants to improve the understanding of the disease aetiology, a GWAS meta-analysis in cases with a diagnosis at ≤35 years of age was performed. MATERIALS AND METHODS: Genotypes from German, Dutch and Spanish GWAS studies of III/IV-C periodontitis diagnosed at age ≤35 years were imputed using TopMed. After quality control, a meta-analysis was conducted on 8,666,460 variants in 1306 cases and 7817 controls with METAL. Variants were prioritized using FUMA for gene-based tests, functional annotation and a transcriptome-wide association study integrating eQTL data. RESULTS: The study identified a novel genome-wide significant association in the FCER1G gene (p = 1.0 × 10-9 ), which was previously suggestively associated with III/IV-C periodontitis. Six additional genes showed suggestive association with p < 10-5 , including the known risk gene SIGLEC5. HMCN2 showed the second strongest association in this study (p = 6.1 × 10-8 ). CONCLUSIONS: This study expands the set of known genetic loci for severe periodontitis with an age of onset ≤35 years. The putative functions ascribed to the associated genes highlight the significance of oral barrier tissue stability, wound healing and tissue regeneration in the aetiology of these periodontitis forms and suggest the importance of tissue regeneration in maintaining oral health.

Complications and treatment errors related to regenerative periodontal surgery.

Regenerative periodontal surgical procedures are an important component in the treatment of advanced periodontitis. They aim to improve the long-term prognosis of teeth that are periodontally compromised by the presence of intrabony and/or furcation defects, resulting biologically in formation of root cementum, periodontal ligament, and alveolar bone and evidenced clinically by reduction of deep pockets to maintainable probing depths and/or improvements of vertical and horizontal furcation depth. Over the last 25 years, substantial clinical evidence has been accumulated to support the value of regenerative procedures in periodontally compromised dentitions. However, treatment success requires close attention to certain factors on the level of the patient, the tooth/defect, and the operator. Ignoring these factors in case selection, treatment planning, and treatment execution will increase the risk of complications that may jeopardize clinical success and may even be considered as treatment errors. Based on the currently available evidence from clinical practice guidelines, treatment algorithms, and on expert opinion, the present article provides an overview on the main factors, which influence the outcomes of regenerative periodontal surgery and gives recommendations on how to prevent complications and treatment errors.

Complications and treatment errors involving periodontal tissues related to orthodontic therapy.

In this review, typical clinical complications involving periodontal tissues are illustrated that can be encountered in conjunction with orthodontic therapy (OT). Special considerations are given for various clinical scenarios, such as the patient presenting in periodontal health, with periodontitis, or with mucogingival conditions. While some of the complications are seen as common side effects of OT, other, more severe, problems that could have been avoided may be viewed as treatment errors. Recommendations are made on how to prevent these complications, based on the currently available evidence, on clinical practice guidelines, and on expert opinion. In conclusion, while there are several areas in which OT can have unwanted adverse effects on periodontal/mucogingival conditions, there is also great potential for synergies, offering opportunities for close cooperation between the two specialties (periodontics and orthodontics) for the benefit of patients affected by tooth malpositioning and/or periodontal or mucogingival problems.

Efficacy of mechanical/physical approaches for implant surface decontamination in non-surgical submarginal instrumentation of peri-implantitis. A systematic review.

AIM: To evaluate the efficacy of non-surgical submarginal peri-implant instrumentation with mechanical/physical decontamination compared to non-surgical submarginal instrumentation alone or with placebo decontamination in patients with peri-implantitis. MATERIALS AND METHODS: Three focused questions were addressed, and a systematic search for randomized controlled clinical trials (RCTs), controlled clinical trials, and prospective cohort studies with definitions of peri-implantitis and a minimal follow-up of 6 months was conducted. The main outcome variables were reduction in pocket probing depth (PD) and bleeding on probing (BOP). Suppuration on probing, marginal peri-implant bone level changes, patient-related outcomes and adverse events, implant survival, treatment success, and disease resolution were assessed as secondary outcomes. RESULTS: Out of 239 findings, full-text articles were assessed for eligibility, and 9 (n = 9 RCTs) were included in the present review. Five studies evaluated the effects of various laser types, and in four studies efficacy of air-abrasive mechanisms and of a novel ultrasonic device was determined. At 6 months, PD reductions were observed in nine studies but only Er, Cr:YSGG laser-treated group showed statistically significant higher reductions compared to the control group. BOP was statistically significantly reduced at 6 months in two studies following the application of Er:YAG laser compared to controls. One study reported statistically significant reduction in BOP following application of air-polishing device compared to control treatment. No statistically significant differences between treatment groups were reported for the secondary outcome variables. Owing to the large heterogeneity of study designs, no meta-analysis was performed. CONCLUSIONS: Available evidence on the efficacy of non-surgical submarginal peri-implant instrumentation with mechanical/physical decontamination is limited by the small number of controlled studies and the high heterogeneity of study protocols. Clinical and patient-reported benefits remain to be demonstrated.

Efficacy of professionally administered chemical agents as an adjunctive treatment to sub-marginal instrumentation during the therapy of peri-implant mucositis.

AIM: To evaluate the efficacy of professionally administered chemical agents as an adjunctive treatment to sub-marginal instrumentation (SMI) in the therapy of peri-implant mucositis. MATERIALS AND METHODS: The primary outcome criteria were reduction in bleeding on probing (BOP), whereas resolution of disease, elimination of suppuration, including suppuration on probing, reduction of peri-implant probing pocket depth, reduction of plaque, and patient-reported outcome measures were considered as secondary outcome parameters. A literature search was performed on three electronic databases (01/1980 to 05/2022) focused on clinical studies with at least 3 months of follow-up, and meta-analyses were performed when appropriate. RESULTS: From a total of 139 publications, 40 articles were identified for full-text reading, and 5 randomized controlled clinical trials (RCTs) on antimicrobial photodynamic therapy (aPDT), 1 RCT on chlorhexidine (CHX), and 1 RCT on sodium hypochlorite (NaOCl) were included. Three studies had a low risk of bias and four had a mid-level (some concerns) risk of bias. The application of aPDT, 0.95% NaOCl, or 0.12% CHX as an adjunctive treatment to SMI showed no difference in changes in BOP and PD compared with SMI alone (p > .05). CONCLUSIONS: Within the limitations of this review and based on a low level of evidence from seven RCTs, it is concluded that the professional adjunctive topical application of aPDT, 0.95% NaOCl, and 0.12% CHX may not be effective to improve changes for BOP and PD when compared with SMI alone.

Prevention and treatment of peri-implant diseases-The EFP S3 level clinical practice guideline.

BACKGROUND: The recently published Clinical Practice Guidelines (CPGs) for the treatment of stages I-IV periodontitis provided evidence-based recommendations for treating periodontitis patients, defined according to the 2018 classification. Peri-implant diseases were also re-defined in the 2018 classification. It is well established that both peri-implant mucositis and peri-implantitis are highly prevalent. In addition, peri-implantitis is particularly challenging to manage and is accompanied by significant morbidity. AIM: To develop an S3 level CPG for the prevention and treatment of peri-implant diseases, focusing on the implementation of interdisciplinary approaches required to prevent the development of peri-implant diseases or their recurrence, and to treat/rehabilitate patients with dental implants following the development of peri-implant diseases. MATERIALS AND METHODS: This S3 level CPG was developed by the European Federation of Periodontology, following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, formulation of specific recommendations, and a structured consensus process involving leading experts and a broad base of stakeholders. RESULTS: The S3 level CPG for the prevention and treatment of peri-implant diseases culminated in the recommendation for implementation of various different interventions before, during and after implant placement/loading. Prevention of peri-implant diseases should commence when dental implants are planned, surgically placed and prosthetically loaded. Once the implants are loaded and in function, a supportive peri-implant care programme should be structured, including periodical assessment of peri-implant tissue health. If peri-implant mucositis or peri-implantitis are detected, appropriate treatments for their management must be rendered. CONCLUSION: The present S3 level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to maintain healthy peri-implant tissues, and to manage peri-implant diseases, according to the available evidence at the time of publication.

Association between periodontal diseases and cardiovascular diseases, diabetes and respiratory diseases: Consensus report of the Joint Workshop by the European Federation of Periodontology (EFP) and the European arm of the World Organization of Family Doctors (WONCA Europe).

AIM: To explore the implications for dentists and family doctors of the association between periodontal and systemic diseases and the role of dentists and family doctors in managing non-communicable diseases (NCDs) and promoting healthy lifestyles. MATERIALS AND METHODS: The consensus reports of the previous Focused Workshops on the associations between periodontitis and diabetes (2017) and periodontitis and cardiovascular diseases (2019) formed the technical reviews to underpin discussions on both topics. For the association with respiratory diseases, a systematic review was specifically commissioned for the Workshop discussions. Working groups prepared proposals independently, and then the proposals were discussed and approved at plenary meetings. RESULTS: Periodontitis is independently associated with cardiovascular diseases, diabetes, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea and COVID-19 complications. Dentists and family doctors should collaborate in managing NCDs, implementing strategies for early detection of periodontitis in primary care centres and of cardiovascular diseases or diabetes in dental settings. Family doctors should be informed about periodontal diseases and their consequences, and oral health professionals (OHPs) should be informed about the relevance of NCDs and the associated risk factors. CONCLUSIONS: Closer collaboration between OHPs and family doctors is important in the early detection and management of NCDs and in promoting healthy lifestyles. Pathways for early case detection of periodontitis in family medicine practices and of NCDs in dental practices should be developed and evaluated.

Prevention of internal bacterial colonization of dental implants: A comparative longitudinal observational study.

OBJECTIVES: Previous studies have indicated a progressive internal bacterial colonization of implants and possible implications for peri-implant bone loss. The aim of this study was to evaluate a decontamination protocol, two disinfectants, and a sealant for their ability to prevent such a colonization. MATERIALS AND METHODS: Bacterial samples were harvested from the peri-implant sulcus (external) and following abutment removal from the implant cavity (internal) during routine supportive peri-implant care in 30 edentulous patients 2 years after they had obtained two implants. In a split-mouth design, implants were randomly assigned to receive either internal decontamination alone (10% H2 O2 , brush) or additional placement of either sealant (GS), disinfectant agent (CHX-varnish) or disinfectant gel (1% CHX-gel), in the internal cavity before remounting of abutment/suprastructure. Twelve months later, internal and external sampling was repeated. Total bacterial counts (TBCs) were determined using real-time PCR in a total of 240 samples (eight per patient). RESULTS: Total bacterial counts in the internal cavity significantly reduced overall treatment modalities 1 year after the treatments (4.0 [2.3-6.9]-fold reduction; p = .000). No significant differences between the four treatment types were found (p = .348). Comparison of internal and external sampling points revealed significant correlation (R2 = .366; p = .000) with systematically higher TBC counts in external samples. CONCLUSIONS: Within the limitations of the present study, it can be concluded that the use of disinfectant agents or a sealant did not show an additional benefit in the prevention of internal bacterial colonization of implants compared to a decontamination protocol alone.

Effects of histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors on proliferative, differentiative, and regenerative functions of Toll-like receptor 2 (TLR-2)-stimulated human dental pulp cells (hDPCs).

OBJECTIVES: This in vitro study aimed to modify TLR-2-mediated effects on the paracrine, proliferative, and differentiation potentials of human dental pulp-derived cells using histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors. MATERIALS AND METHODS: Cell viability was assessed using the XTT assay. Cells were either treated with 10 µg/ml Pam3CSK4 only, or pre-treated with valproic acid (VPA) (3 mM), trichostatin A (TSA) (3 µM), and MG-149 (3 µM) for a total of 4 h and 24 h. Control groups included unstimulated cells and cells incubated with inhibitors solvents only. Transcript levels for NANOG, OCT3-4, FGF-1 and 2, NGF, VEGF, COL-1A1, TLR-2, hßD-2 and 3, BMP-2, DSPP, and ALP were assessed through qPCR. RESULTS: After 24 h, TSA pre-treatment significantly upregulated the defensins and maintained the elevated pro-inflammatory cytokines, but significantly reduced healing and differentiation genes. VPA significantly upregulated the pro-inflammatory cytokine levels, while MG-149 significantly downregulated them. Pluripotency genes were not significantly affected by any regimen. CONCLUSIONS: At the attempted concentrations, TSA upregulated the defensins gene expression levels, and MG-149 exerted a remarkable anti-inflammatory effect; therefore, they could favorably impact the immunological profile of hDPCs. CLINICAL RELEVANCE: Targeting hDPC nuclear function could be a promising option in the scope of the biological management of inflammatory pulp diseases.

Biomechanical properties of periodontal tissues in non-periodontitis and periodontitis patients assessed with an intraoral computerized electronic measurement device.

OBJECTIVE: To identify tooth mobility (TM) by time-dependent tooth displacement using an electronic intra-oral loading device (ILD) in periodontally healthy and periodontally compromised patients. MATERIALS AND METHODS: Twenty-eight untreated periodontitis and 20 periodontally healthy patients [25 female and 26 male; ages: 20-81 years], contributing with 68 teeth (periodontitis: nteeth = 28; non-periodontitis: nteeth = 40), participated in the study. TM was measured in vivo by displacing central or lateral incisors to a maximum of 0.2 mm orally over durations of 0.5 s, 1 s, and 10 s with the ILD. The maximum force (Fmax) was extracted from the measured force/deflection curves for every single measurement. RESULTS: Differences in TM-ILD values were found for periodontitis as compared to non-periodontitis patients derived from the same loading durations (differences of 3.9 (0.5 s), 3.1 (1 s), 2.8 (10 s), (95% CI for 0.5 s (1.2-6.7), p = 0.024; 1 s (1.4-6.0), p = 0.067; 10 s (0.2-5.3), p = 0.001), rejecting the null hypothesis of no difference (T-test) for durations of 0.5 and 10 s. There was a significant correlation of TM-ILD (Fmax) with BOP at 0.5 s (- 0.52) and with attachment loss at all time durations (- 0.47 at 0.5 s; - 0.57 at 1 s; - 0.47 at 10 s). CONCLUSIONS: This clinical investigation could demonstrate that time-dependent tooth displacements using a new computerized electronic device were associated with attachment loss and bleeding on probing. CLINICAL RELEVANCE: ILD can improve the monitoring of tooth mobility, as TM-ILD values reflect qualitative (inflammatory status interpreted by BOP) and quantitative parameters (interpreted as the amount of CAL loss) of periodontal disease.

Reliability of probing depth assessments at healthy implant sites and natural teeth.

AIM: To evaluate the intra- and inter-examiner reliability in the assessment of probing depth (PD) measurements at healthy dental implant sites and periodontally healthy natural teeth. MATERIALS AND METHODS: Five patients exhibiting 21 dental implants were enrolled in the study. Eight experienced examiners performed duplicate PD measurements at six sites of all implants and of preselected natural teeth. Intra-examiner accuracy was estimated using intra-examiner correlation coefficients (ICCs) with 95% confidence intervals (CI). A gold standard (GS) examiner was set. Inter-examiner accuracy compared to the GS examiner was assessed using pairwise inter-examiner ICCs. RESULTS: The intra-examiner ICC ranged from 0.759 (95% CI, 0.692-0.812) to 0.863 (95% CI, 0.826-0.892) for the measurements at teeth and from 0.712 (95% CI, 0.580-0.800) to 0.841 (95% CI, 0.774-0.888) for the PDs assessed at implants. The inter-examiner ICCs for tooth measurements varied from 0.197 (95% CI, - 0.280 to 0.511) to 0.791 (95% CI, 0.560-0.892). The corresponding values for the assessments at implants varied from 0.576 (95% CI, 0.286-0.734) to 0.794 (95% CI, 0.708-0.855). CONCLUSIONS: The intra- and inter-examiner reproducibility of repeated PD measurements assessed by experienced examiners tended to be higher for the measurements at periodontally healthy teeth compared to healthy dental implant sites. CLINICAL RELEVANCE: Experienced examiners demonstrated a higher degree of reliability of probing measurements around teeth compared to dental implants.

Surgical therapy of peri-implantitis.

Peri-implantitis is caused by a bacterial challenge; therefore, anti-infective treatment strategies should be employed to manage the disease. As nonsurgical approaches demonstrate limited efficacy in most cases of peri-implantitis, surgical interventions are often required. Treatment outcomes improve following access flap surgery, with or without adjunctive resective and/or augmentation measures. Whereas nonaugmentative therapies (ie, access flap surgery and resective techniques) primarily aim to resolve inflammation and arrest further disease progression, augmentation approaches also seek to regenerate the bony defect and achieve reosseointegration. Currently, limited evidence supports the superiority of augmentative surgical techniques for peri-implantitis treatment over nonaugmentation methods, and human histologic evidence for reosseointegration is sparse. For patients involved in regular postoperative maintenance programs, success of peri-implantitis surgical treatment based on various definitions of success was obtained in over half of the cases after 5-7 years. Despite surgical treatment, cases of further disease progression that required retreatment or led to implant loss were reported.

Efficacy of tooth splinting and occlusal adjustment in patients with periodontitis exhibiting masticatory dysfunction: A systematic review.

OBJECTIVE: To evaluate the efficacy of tooth splinting (TS) and occlusal adjustment (OA) compared to no TS or OA in patients with periodontitis exhibiting masticatory dysfunction. MATERIAL: The primary outcome criterion was tooth loss (TL), and the secondary outcome parameters were change in probing pocket depth (PPD), change in clinical attachment level (CAL), tooth mobility (TM), and patient-reported outcome measures (PROMs). Literature search was performed on three electronic databases (from 01/1965 to 04/2021) and focused on clinical studies with at least 12 months follow-up. RESULTS: From a total of 1515 publications, 51 articles were identified for full-text reading, of which 2 retrospective case series on TS with low risk of bias and 1 randomized and 2 prospective studies on OA with unclear risk of bias were included. For TS, synthesis of data showed that in 72 patients, 26 out of 311 teeth (weighted mean incidence of TL 8.4%) and 156 out of 1541 teeth with no TS (weighted mean incidence of TL 10.1%) were lost over 2 years following non-surgical periodontal therapy. The randomized controlled clinical trial (RCT) indicated CAL gain for teeth with OA compared to no OA. For the effect of OA on TL, PPD, and TM, heterogeneous data were retrieved from the included studies. CONCLUSIONS: Within the limitations of this review and based on a low level of evidence, it is concluded that TS does not improve survival of mobile teeth in patients with advanced periodontitis. OA on teeth with mobility and/or premature contacts may lead to improved CAL, while the effect of OA on the remaining periodontal parameters remains unclear.

Treatment of stage IV periodontitis: The EFP S3 level clinical practice guideline.

BACKGROUND: The recently published clinical practice guideline (CPG) for the treatment of periodontitis in stages I-III provided evidence-based recommendations for the treatment of periodontitis patients, defined according to the 2018 classification. Stage IV periodontitis shares the severity and complexity characteristics of stage III periodontitis, but includes the anatomical and functional sequelae of tooth and periodontal attachment loss (tooth flaring and drifting, bite collapse, etc.), which require additional interventions following completion of active periodontal therapy. AIM: To develop an S3 Level CPG for the treatment of stage IV periodontitis, focusing on the implementation of inter-disciplinary treatment approaches required to treat/rehabilitate patients following associated sequelae and tooth loss. MATERIALS AND METHODS: This S3 Level CPG was developed by the European Federation of Periodontology (EFP), following methodological guidance from the Association of Scientific Medical Societies in Germany and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process. A rigorous and transparent process included synthesis of relevant research in 13 specifically commissioned systematic reviews, evaluation of the quality and strength of evidence, the formulation of specific recommendations and a structured consensus process with leading experts and a broad base of stakeholders. RESULTS: The S3 Level CPG for the treatment of stage IV periodontitis culminated in recommendations for different interventions, including orthodontic tooth movement, tooth splinting, occlusal adjustment, tooth- or implant-supported fixed or removable dental prostheses and supportive periodontal care. Prior to treatment planning, it is critically important to undertake a definitive and comprehensive diagnosis and case evaluation, obtain relevant patient information, and engage in frequent re-evaluations during and after treatment. The periodontal component of therapy should follow the CPG for the treatment of periodontitis in stages I-III. CONCLUSIONS: The present S3 Level CPG informs clinical practice, health systems, policymakers and, indirectly, the public on the available and most effective modalities to treat patients with stage IV periodontitis and to maintain a healthy dentition over lifetime, according to the available evidence at the time of publication.

Clinical, microbiological, and immunological effects of 3- or 7-day systemic antibiotics adjunctive to subgingival instrumentation in patients with aggressive (Stage III/IV Grade C) periodontitis: A randomized placebo-controlled clinical trial.

AIM: To evaluate the clinical non-inferiority of a 3-day protocol of systemic antibiotics adjunctive to subgingival instrumentation (SI) compared with a 7-day-protocol in patients with Stage III/IV Grade C periodontitis. MATERIALS AND METHODS: Fifty systemically healthy patients (32.7 ± 4.3 years) with aggressive periodontitis (AgP; Stage III/IV Grade C periodontitis) were treated by SI and adjunctive amoxicillin and metronidazole and were randomly assigned to Group A: (n = 25) 500 mg antibiotics (AB) 3 times a day for 3 days, followed by placebo 3 times a day for 4 days, or Group B: (n = 25) 500 mg AB 3 times a day for 7 days. Clinical, microbial, and immunological parameters were assessed at baseline, 3 months, and 6 months, and patient-related outcomes were assessed after 2 weeks. The primary outcome variable was the number of residual sites with pocket depth (PD) ≥6 mm at 6 months. RESULTS: For the primary outcome variable (the number of residual sites with PD ≥6 mm at 6 months), the null hypothesis was rejected and non-inferiority of the 3-day AB protocol compared with the 7-day AB protocol was demonstrated (the upper limits of the 95% confidence interval for intention to treat analysis: [-2.572; 1.050] and per protocol analysis: [-2.523; 1.318] were lower than the assumed margin of Δ = 3.1). Comparable clinical improvements were obtained for all parameters with both antibiotic protocols (p > .05). All investigated periodontopathogens and pro-inflammatory host-derived markers were statistically significantly reduced without differences between the treatments (p > .05). CONCLUSIONS: These findings indicate that in patients with AgP (Stage III/IV Grade C periodontitis), a 3-day systemic administration of amoxicillin and metronidazole adjunctive to SI may lead to non-inferior clinical outcomes after 6-months with fewer adverse events compared with a 7-day-protocol.

Full-mouth treatment modalities (within 24 hours) for periodontitis in adults.

BACKGROUND: Periodontitis is a highly prevalent, chronic inflammation that causes damage to the soft tissues and bones supporting the teeth. Conventional treatment is quadrant scaling and root planing (the second step of periodontal therapy), which comprises scaling and root planing of teeth in one quadrant of the mouth at a time, with the four different sessions separated by at least one week. Alternative protocols for anti-infective periodontal therapy have been introduced to help enhance treatment outcomes: full-mouth scaling (subgingival instrumentation of all quadrants within 24 hours), or full-mouth disinfection (subgingival instrumentation of all quadrants in 24 hours plus adjunctive antiseptic). We use the older term 'scaling and root planing' (SRP) interchangeably with the newer term 'subgingival instrumentation' in this iteration of the review, which updates one originally published in 2008 and first updated in 2015. OBJECTIVES: To evaluate the clinical effects of full-mouth scaling or full-mouth disinfection (within 24 hours) for the treatment of periodontitis compared to conventional quadrant subgingival instrumentation (over a series of visits at least one week apart) and to evaluate whether there was a difference in clinical effects between full-mouth disinfection and full-mouth scaling. SEARCH METHODS: An information specialist searched five databases up to 17 June 2021 and used additional search methods to identify published, unpublished and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) lasting at least three months that evaluated full-mouth scaling and root planing within 24 hours, with or without adjunctive use of an antiseptic, compared to conventional quadrant SRP (control). Participants had a clinical diagnosis of (chronic) periodontitis according to the International Classification of Periodontal Diseases from 1999. A new periodontitis classification was launched in 2018; however, we used the 1999 classification for inclusion or exclusion of studies, as most studies used it. We excluded studies of people with systemic disorders, taking antibiotics or with the older diagnosis of 'aggressive periodontitis'. DATA COLLECTION AND ANALYSIS: Several review authors independently conducted data extraction and risk of bias assessment (based on randomisation method, allocation concealment, examiner blinding and completeness of follow-up). Our primary outcomes were tooth loss and change in probing pocket depth (PPD); secondary outcomes were change in probing attachment (i.e. clinical attachment level (CAL)), bleeding on probing (BOP), adverse events and pocket closure (the number/proportion of sites with PPD of 4 mm or less after treatment). We followed Cochrane's methodological guidelines for data extraction and analysis. MAIN RESULTS: We included 20 RCTs, with 944 participants, in this updated review. No studies assessed the primary outcome tooth loss. Thirteen trials compared full-mouth scaling and root planing within 24 hours without the use of antiseptic (FMS) versus control, 13 trials compared full-mouth scaling and root planing within 24 hours with adjunctive use of an antiseptic (FMD) versus control, and six trials compared FMS with FMD. Of the 13 trials comparing FMS versus control, we assessed three at high risk of bias, six at low risk of bias and four at unclear risk of bias. We assessed our certainty about the evidence as low or very low for the outcomes in this comparison. There was no evidence for a benefit for FMS over control for change in PPD, gain in CAL or reduction in BOP at six to eight months (PPD: mean difference (MD) 0.03 mm, 95% confidence interval (CI) -0.14 to 0.20; 5 trials, 148 participants; CAL: MD 0.10 mm, 95% CI -0.05 to 0.26; 5 trials, 148 participants; BOP: MD 2.64%, 95% CI -8.81 to 14.09; 3 trials, 80 participants). There was evidence of heterogeneity for BOP (I² = 50%), but none for PPD and CAL. Of the 13 trials comparing FMD versus control, we judged four at high risk of bias, one at low risk of bias and eight at unclear risk of bias. At six to eight months, there was no evidence for a benefit for FMD over control for change in PPD or CAL (PPD: MD 0.11 mm, 95% CI -0.04 to 0.27; 6 trials, 224 participants; low-certainty evidence; CAL: 0.07 mm, 95% CI -0.11 to 0.24; 6 trials, 224 participants; low-certainty evidence). The analyses found no evidence of a benefit for FMD over control for BOP (very low-certainty evidence). There was no evidence of heterogeneity for PPD or CAL, but considerable evidence of heterogeneity for BOP, attributed to one study. There were no consistent differences in these outcomes between intervention and control (low- to very low-certainty evidence). Of the six trials comparing FMS and FMD, we judged two trials at high risk of bias, one at low risk of bias and three as unclear. At six to eight months, there was no evidence of a benefit of FMD over FMS for change in PPD or gain in CAL (PPD: MD -0.11 mm, 95% CI -0.30 to 0.07; P = 0.22; 4 trials, 112 participants; low-certainty evidence; CAL: MD -0.05 mm, 95% CI -0.23 to -0.13; P = 0.58; 4 trials, 112 participants; low-certainty evidence). There was no evidence of a difference between FMS and FMD for BOP at any time point (P = 0.98; 2 trials, 22 participants; low- to very low-certainty evidence). There was evidence of heterogeneity for BOP (I² = 52%), but not for PPD or CAL. Thirteen studies predefined adverse events as an outcome; three reported an event after FMD or FMS. The most important harm identified was an increase in body temperature. We assessed the certainty of the evidence for most comparisons and outcomes as low because of design limitations leading to risk of bias, and the small number of trials and participants, leading to imprecision in the effect estimates. AUTHORS' CONCLUSIONS: The inclusion of nine new RCTs in this updated review has not changed the conclusions of the previous version of the review. There is still no clear evidence that FMS or FMD approaches provide additional clinical benefit compared to conventional mechanical treatment for adult periodontitis. In practice, the decision to select one approach to non-surgical periodontal therapy over another should include patient preference and the convenience of the treatment schedule.

Fecal calprotectin as a biomarker of intestinal inflammation in ICU patients with diarrhea - testing the pipette method against the collection pin and weighing methods.

Fecal calprotectin is an established biomarker in inflammatory bowel disease, but its role in assessment of intestinal inflammation in ICU patients is yet to be explored. ICU patients tend to acquire diarrhea, which complicates the extraction of fecal calprotectin using a collection pin for stool sampling. Pipetting is an alternative sampling method. The aim of the study was to compare the collection pin method with the pipette method for measurement of fecal calprotectin in ICU patients with diarrhea. Stool samples were collected from fecal bags used in the patients and then analyzed for calprotectin using an extraction device and a piston pipette, respectively. In addition, a validation test for the pipette method of extraction was conducted on liquid stool samples. Eleven stool samples were collected from five randomly selected ICU patients. Calprotectin was detectable in all fecal samples. On average the collection pin measured 45% lower than the pipette method with a 95% confidence interval (30 - 59%). The coefficient of variation when using the pipette method was 13% in low calprotectin concentrations and 39% in high concentrations. In conclusion, the pipette method seems to be appropriate for measuring calprotectin in liquid feces, due to practicalities and a greater precision.